Cytokine receptor dephosphorylation molecules target therapy for rejection after lung transplantation

• Project/Area Number: 24592089
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Osaka University
• Principal Investigator: NAKAGIRI Tomoyuki 大阪大学, 医学(系)研究科(研究院), 招へい教員 (70528710)
• Co-Investigator(Kenkyū-buntansha): MINAMI Masato 大阪大学, 医学部附属病院, 手術部教授 (10240847) ; INOUE Masayoshi 大阪大学大学院医学系研究科外科学講座, 呼吸器外科, 准教授 (10379232) ; OKUMURA Meinoshin 大阪大学大学院医学系研究科外科学講座, 呼吸器外科, 教授 (40252647) ; SHINTANI Yasushi 大阪大学大学院医学系研究科外科学講座, 呼吸器外科, 講師 (90572983) ; KAWAMURA Tomohiro 大阪大学大学院医学系研究科外科学講座, 呼吸器外科, 助教 (30528675) ; 澤端 章好 大阪大学, 医学(系)研究科(研究院), 教授 (50403184)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: 肺移植 / 慢性拒絶 / 分子標的治療 / 分子標的療法 / IL-6 / Th17 / 抗リン酸化

Outline of Final Research Achievements

The largest reason to decide long-term outcome after the lung transplantation is chronic rejection. The chronic rejection after the lung transplantation is diagnosed as existence of bronchiolitis obliterans (BO), pathologically. However, the formation mechanism, suppression method, and the treatment are still unknown.
We previously revealed that IL-6 affected the BO formation. As for the IL-6 receptor, the signal transmission is made by STAT3. We hypothesized that we could control the BO formation by restraint by activation of STAT3. After searching for the inhibitor using mouse BO model, it was suggested that the BO formation was reduced by the zinc administration. However, the mechanism of the inhibition was still unknown. We continue this study of the mechanism elucidation.

Research Products

• [Journal Article] Improved procedures and comparative results for video-assisted thoracoscopic extended thymectomy for myasthenia gravis. (2014)
  • Author(s): Nakagiri T, Inoue M, Shintani Y, Funaki S, Kawamura T, Minami M, Ohta M, Kadota Y, Shiono H, Okumura M.
  • Journal Title: Surg Endosc. Volume: E-pub
  • Peer Reviewed
• [Journal Article] Evaluation of the new IASLC/ATS/ERS proposed classification of adenocarcinoma based on lepidic pattern in patients with pathological stage IA pulmonary adenocarcinoma. (2014)
  • Author(s): Nakagiri T, Sawabata N, Morii E, Inoue M, Shintani Y, Funaki S, Okumura M.
  • Journal Title: Gen Thorac Cardiovasc Surg. Volume: 62 Issue: 11 Pages: 671-7
  • DOI: 10.1007/s11748-014-0429-3
  • Peer Reviewed
• [Journal Article] Results of surveillance bronchoscopy after cadaveric lung transplantation: a Japanese single-institution study. (2014)
  • Author(s): Inoue M, Minami M, Wada N, Nakagiri T, Funaki S, Kawamura T, Shintani Y, Okumura M.
  • Journal Title: Transplant Proc. Volume: 46 Issue: 3 Pages: 944-7
  • DOI: 10.1016/j.transproceed.2013.10.055
  • Peer Reviewed
• [Journal Article] Does Gefitinib Have Effects on EGFR Mutation-Positive Thymoma? —Case Report of Thymoma Recurrence (2014)
  • Author(s): Nakagiri T, Funaki S, Kadota Y, Takeuchi Y, Shiono H, Akashi A, Okumura M.
  • Journal Title: Annals of Thoracic and Cardiovascular Surgery Volume: 20 Issue: Supplement Pages: 674-676
  • DOI: 10.5761/atcs.cr.13-00141
  • NAID: 130003396746
  • ISSN: 1341-1098, 2186-1005
  • Peer Reviewed
• [Journal Article] Interim report of the Japanese original donor evaluation and management system: the medical consultant system. (2014)
  • Author(s): Nakagiri T, Inoue M, Minami M, Hoshikawa Y, Chida M, Bando T, Oto T, Shiraishi T, Yamasaki N, Ashikari J, Sawa Y, Okumura M.
  • Journal Title: Surg Today Volume: 44 Pages: 1227-31
  • Peer Reviewed
• [Journal Article] Does gefitinib have effects on EGFR mutation-positive thymoma? – Case report of thymoma recurrence (2014)
  • Author(s): Nakagiri T, Soichiro Funaki, Yoshihisa Kadota, Yukiyasu Takeuchi, Hiroyuki Shiono, Akinori Akashi, Meinoshin Okumura
  • Journal Title: Annals Thoracic and Cardiovascular Surgery Volume: E-pub
  • NAID: 130003396746
  • Peer Reviewed
• [Journal Article] IL-6 amplifier activation in epitherial resions of bronchi after allogenic lung transplantation (2013)
  • Author(s): Lee J, Nakagiri T, Kamimura D, Harada M, Oto T, Susaki Y, Shintani Y, Inoue M, Miyoshi S, Morii E, Hirano T, Murakami M, Okumura M
  • Journal Title: International Immunology Volume: 25 Pages: 319-332
  • Peer Reviewed
• [Journal Article] Huge thymoma obstructing view of mediastinal cervical vessels (2013)
  • Author(s): Nakagiri T, Okumura M
  • Journal Title: Clinical Case Reports Volume: 15 Pages: 1-2
  • Peer Reviewed
• [Journal Article] Risk of major hemorrhage in bilateral lung transplantation for chronic thromboemlic pulmonary hypertention: a case report (2013)
  • Author(s): Nakagiri T, Minami M, Inoue M, Funaki S, Shintani Y, Okumura M
  • Journal Title: Open Journal of Ogan Transplant Surgery Volume: 3 Pages: 65-67
  • Peer Reviewed
• [Journal Article] Inoue M, Minami M, Hoshikawa Y, Chida M, Bando T, Oto T, Shiraishi T, Yamasaki N, Ashkari J, Sawa Y, Okumura M (2013)
  • Author(s): Nakagiri T,
  • Journal Title: Surgery Today Volume: E-pub
  • Peer Reviewed
• [Journal Article] IL-6 amplifier activation in epithelial regions of bronchi after allogeneic lung transplantation. (2013)
  • Author(s): Lee J, Nakagiri T, Kamimura D, Harada M, Oto T, Susaki Y, Shintani Y, Inoue M, Miyoshi S, Morii E, Hirano T, Murakami M, Okumura M.
  • Journal Title: Int Immunol. Volume: Epub
• [Journal Article] IL-6 amplifier, NF-κB-triggered positive feedback for IL-6 signaling, in grafts is involved in allogeneic rejection responses. (2012)
  • Author(s): Lee J
  • Journal Title: Journal of Immunology Volume: 189 Issue: 4 Pages: 1928-1936
  • DOI: 10.4049/jimmunol.1103613
  • Peer Reviewed
• [Presentation] Zinc Suppresses Pathogenesis of Bronchiolitis Obliterans via Inhibition of IL-6 receptor (2012)
  • Author(s): Tomoyuki Nakagiri, Yasushi Shintani, Masayoshi Inoue, Masato Minami, Noriyoshi Sawabata, Meinoshin Okumura
  • Organizer: ISHLT 2012 第32回国際心肺移植学会議
  • Place of Presentation: チェコ
• [Presentation] 肺メディカル・コンサルタント（MC)の導入―その現状と課題―
  • Author(s): 中桐伴行、芦刈淳太郎、奥村明之進
  • Organizer: 日本肺および心肺移植研究会(29)
  • Place of Presentation: 千葉
• [Presentation] 慢性血栓塞栓性肺高血圧症に対する脳死両肺移植に際し、大量出血を来たし頻回の開胸止血術を要した一例
  • Author(s): 中桐伴行、南 正人、井上匡美、須崎剛行、舟木壮一郎、新谷 康、澤端章好、奥村明之進
  • Organizer: 日本呼吸器外科学会総会(30)
  • Place of Presentation: 名古屋
• [Presentation] リンパ脈管筋腫症(LAM)に対する肺移植後の晩期合併症
  • Author(s): 中桐伴行、南 正人、井上匡美、新谷 康、舟木壮一郎、川村知裕、澤端章好、奥村明之進
  • Organizer: 日本移植学会総会(49)
  • Place of Presentation: 京都
• [Presentation] 肺移植後の気管支上皮におけるIL-6増幅回路の活性
  • Author(s): 中桐伴行、李 智慧、大藤剛宏、井上匡美、森井英一、平野俊夫、村上正晃、奥村明之進
  • Organizer: 日本移植学会総会(49)
  • Place of Presentation: 京都
• [Presentation] 胸腔鏡下拡大胸腺摘出術における胸腺摘出範囲と手順について
  • Author(s): 中桐伴行、井上匡美、新谷 康、舟木壮一郎、川村知裕、澤端章好、南 正人、奥村明之進
  • Organizer: 呼吸器胸腔鏡手術手技研究会(13)
  • Place of Presentation: 福岡
• [Presentation] 異系移植拒絶におけるIL-6 増幅回路の役割
  • Author(s): 中桐伴行、李 智慧、原田誠也、高橋勇次 新谷 康、森井英一、大藤剛宏、奥村明之進 平野俊夫、村上正晃
  • Organizer: 肺および心肺移植研究会
  • Place of Presentation: 千葉